157P - Efficacy and safety of penpulimab (AK105), a new generation anti-programmed cell death-1 (PD-1) antibody, in upper gastrointestinal cancers

Background

Upper gastrointestinal (UGI) cancers are a group of highly aggressive malignancies with poor prognoses. Immunotherapy is emerging as an effective treatment option for some of these cancers. Penpulimab, a new generation anti-PD-1 monoclonal antibody, was engineered to optimize receptor occupancy by improving duration of drug binding, and to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function. Here, we present the preliminary antitumor and safety data on Penpulimab in patients (pts) with advanced UGI malignancies.

Methods

Pts with advanced cancers, relapsed or refractory to standard therapy but naïve to immune checkpoint inhibitors (ICIs), were enrolled in two phase I trials of Penpulimab (NCT03352531 and NCT04172506). Pts received Penpulimab IV at 1-10 mg/kg Q2W or 200mg Q2W until disease progression or unacceptable toxicity. Antitumor activity was investigator-assessed per RECIST v1.1 criteria.

Results

As of 1st July 2020, 67 pts with UGI cancers received Penpulimab for a median of 6 (1–64) doses. The antitumor activity of Penpulimab in the 60 pts evaluable for efficacy is shown below. 11/13 (85%) responders had ongoing responses at data cutoff date. Table: 157P

Treatment-related adverse events (TRAEs) occurred in 44.8% of pts. There were no discontinuations due to drug-related AEs or drug-related deaths. Grade ≥3 TRAEs occurred in 5 pts (7.5%) – raised liver enzymes (n=2), adrenal insufficiency (n=1) and hyponatraemia (n=1) in the same pt, intestinal obstruction (n=1), and hypertension (n=1).

Conclusions

Penpulimab was well tolerated and demonstrated encouraging antitumor activity with durable response in pts with advanced UGI cancers, including PCA and CCA, which are generally resistant to single agent ICI. Penpulimab in combination with anlotinib, a multi-targeted receptor tyrosine kinase inhibitor, is being evaluated in phase III studies for 1L HCC (NCT04344158) and 2L Gastric/GEJ (NCT04385550).

Clinical trial identification

NCT03352531; NCT04172506.

Editorial acknowledgement

Legal entity responsible for the study

Akeso Biopharma Inc.

Funding

Akeso Biopharma Inc.

Disclosure

A.R.A. Mislang: Honoraria (self): BMS. A. Cooper: Honoraria (self): MSD; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Roche. X. Jin, K.Y. Kwek: Shareholder/Stockholder/Stock options, Full/Part-time employment: Akeso Biopharma. B. Li, M. Wang, D. Xia: Y. Xia: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Akeso Biopharma. A. Prawira: Research grant/Funding (institution), Non-remunerated activity/ies: Akeso Biopharma; Research grant/Funding (institution), Non-remunerated activity/ies: Beigene; Research grant/Funding (institution), Non-remunerated activity/ies: Corvus; Research grant/Funding (institution), Non-remunerated activity/ies: CStone; Research grant/Funding (institution), Non-remunerated activity/ies: Macrogenics; Research grant/Funding (institution), Non-remunerated activity/ies: Five Prime; Research grant/Funding (institution), Non-remunerated activity/ies: Virogin; Research grant/Funding (institution), Non-remunerated activity/ies: QBiotics; Research grant/Funding (institution): Arcusbio; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Apollomics; Research grant/Funding (institution): ENB Therapeutics; Research grant/Funding (institution): Henlius; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): INXMed; Research grant/Funding (institution): Merck/MSD; Research grant/Funding (institution): Janssen. All other authors have declared no conflicts of interest.